A Randomized Placebo-Controlled Phase 2 Study of Gemcitabine and Capecitabine with or without T-ChOS as Adjuvant Therapy in Patients with Resected Pancreatic Cancer (CHIPAC).

YKL-40 adjuvant chemotherapy chitinase 3-like 1 protein chitooligosaccharide pancreatic cancer

Journal

Pharmaceutics
ISSN: 1999-4923
Titre abrégé: Pharmaceutics
Pays: Switzerland
ID NLM: 101534003

Informations de publication

Date de publication:
25 Feb 2022
Historique:
received: 17 01 2022
revised: 17 02 2022
accepted: 23 02 2022
entrez: 26 3 2022
pubmed: 27 3 2022
medline: 27 3 2022
Statut: epublish

Résumé

The antitumor activity of chitooligosaccharides has been suggested. This phase 2 trial evaluated the efficacy and safety of T-ChOS™, in addition to adjuvant chemotherapy, in patients after resection of pancreatic ductal adenocarcinoma (PDAC). In this single-center, randomized, double-blind, placebo-controlled trial using patients ≥18 years of age after complete macroscopic resection for PDAC, patients were randomly assigned (1:1) to either a continuous oral T-ChOS group or a placebo group, in combination with gemcitabine (GEM) and oral capecitabine (CAP), for a maximum of six cycles. The primary endpoint was disease-free survival (DFS). Recruitment was stopped prematurely in July 2018, with 21 of planned 180 patients included, due to poor accrual and because modified FOLFIRINOX replaced GEM/CAP for the target population. Nine patients received T-ChOS and twelve received the placebo. The median DFS was 10.8 months (95% CI 5.9-15.7) for the T-ChOS arm and 8.4 months (95% CI 0-21.5) in the placebo arm. Overall, seven patients (78%) in the T-ChOS arm and eight patients (67%) in the placebo arm experienced at least one grade 3-4 treatment-related adverse event, most frequently neutropenia. Altogether, the addition of T-ChOS to chemotherapy in patients after resection of PDAC seems safe. However, the clinical benefit cannot be assessed due to the premature cessation of the trial.

Identifiants

pubmed: 35335885
pii: pharmaceutics14030509
doi: 10.3390/pharmaceutics14030509
pmc: PMC8955369
pii:
doi:

Types de publication

Journal Article

Langues

eng

Références

Lancet. 2016 Jul 2;388(10039):73-85
pubmed: 26830752
Food Chem Toxicol. 2009 Aug;47(8):1864-71
pubmed: 19427889
J Natl Cancer Inst. 1993 Mar 3;85(5):365-76
pubmed: 8433390
Acta Oncol. 2019 Jun;58(6):864-871
pubmed: 30905248
Acta Oncol. 2016;55(3):265-77
pubmed: 26213211
Nat Rev Clin Oncol. 2018 Apr;15(4):234-248
pubmed: 29405201
Front Microbiol. 2019 Sep 18;10:2101
pubmed: 31620100
J Hematol Oncol. 2017 Feb 1;10(1):36
pubmed: 28143526
Clin Chim Acta. 2011 Apr 11;412(9-10):709-12
pubmed: 21272568
Int J Mol Sci. 2011 Jan 06;12(1):266-77
pubmed: 21339986
Int J Mol Sci. 2010;11(12):5152-64
pubmed: 21614199
Cancer Med. 2016 Oct;5(10):2825-2831
pubmed: 27671746
World J Gastroenterol. 2016 Jun 14;22(22):5193-200
pubmed: 27298562
JAMA. 2013 Oct 9;310(14):1473-81
pubmed: 24104372
Cancer Treat Rev. 2012 Nov;38(7):904-10
pubmed: 22651903
Nature. 2019 Mar;567(7747):249-252
pubmed: 30842658
Biochem Biophys Res Commun. 2013 May 3;434(2):298-304
pubmed: 23541584
Cancer Cell Int. 2019 Oct 10;19:259
pubmed: 31624472
Cell. 2011 Mar 4;144(5):646-74
pubmed: 21376230
JAMA. 2010 Sep 8;304(10):1073-81
pubmed: 20823433
Signal Transduct Target Ther. 2020 Sep 14;5(1):201
pubmed: 32929074
Ann Oncol. 2020 May;31(5):650-658
pubmed: 32321669
Lancet. 2017 Mar 11;389(10073):1011-1024
pubmed: 28129987
CA Cancer J Clin. 2020 Jan;70(1):7-30
pubmed: 31912902
Nat Rev Dis Primers. 2016 Apr 21;2:16022
pubmed: 27158978
Eur J Cancer. 2000 Sep;36(14):1796-807
pubmed: 10974628
N Engl J Med. 2004 Mar 18;350(12):1200-10
pubmed: 15028824
Nat Immunol. 2015 May;16(5):448-57
pubmed: 25898198
Carbohydr Polym. 2021 Aug 15;266:118132
pubmed: 34044948
Ann Surg Oncol. 2019 Nov;26(12):4108-4116
pubmed: 31313044
J Clin Oncol. 2014 Feb 20;32(6):504-12
pubmed: 24419109
Int J Mol Sci. 2018 Jul 27;19(8):
pubmed: 30060500
N Engl J Med. 2018 Dec 20;379(25):2395-2406
pubmed: 30575490
Tumour Biol. 2016 Sep;37(9):11553-11572
pubmed: 27260630
Cancer Lett. 2021 Mar 31;501:210-223
pubmed: 33212158
Biomarkers. 2008 Feb;13(1):59-78
pubmed: 17852075
JAMA. 2007 Jan 17;297(3):267-77
pubmed: 17227978
Asian Pac J Trop Med. 2015 Sep;8(9):757-61
pubmed: 26433663
World J Gastrointest Oncol. 2017 Jul 15;9(7):281-292
pubmed: 28808501
Oncotarget. 2018 Jul 3;9(51):29820-29841
pubmed: 30038723
World J Surg Oncol. 2019 Nov 9;17(1):185
pubmed: 31706323

Auteurs

Susann Theile (S)

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

Julia Sidenius Johansen (JS)

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
Department of Medicine, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

Dorte Lisbet Nielsen (DL)

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.

Benny Vittrup Jensen (BV)

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

Carsten Palnæs Hansen (CP)

Department of Surgery, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

Jane Preuss Hasselby (JP)

Department of Pathology, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark.

Sverrir Vídalín Eiríksson (SV)

Genís hf., 580 Siglufjörður, Iceland.

Inna Markovna Chen (IM)

Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, 2730 Herlev, Denmark.

Classifications MeSH